We would like to study metabolite control of enzymes or its reverse, i,e., enzyme (or enzyme complex) control of metabolite concentrations. Because of our experience, we have concentrated on the arginine-urea and pyrimidine biosynthetic pathways. Studies have and will continue to involve research on both bacterial and mammalian systems with greater emphasis on the latter. Specifically, we will study in appropriate systems: a) the control of these enzymes in unicellular and multicellular organisms; b) the mechanism of the reactions for their own value as well as to aid our understanding of the control mechanisms; c) the chemistry of the enzymes; and d) the in vivo metabolic control of these enzymes in mammals during growth, or in differentiation, or when changes in nutritional state are made, or in abnormal tissues such as cancer cells, or in human mutant cells.